Abstract
Background: PFO allows venous clots and vasoactive circulatory factors to bypass pulmonary filtration and remain in circulation. Serotonin (5-HT) has procoagulant and oxidative roles in both cardiovascular and neurovascular injury. We previously identified an immediate reduction of 5-HT in left atrial blood post PFO closure. To understand the long-term effect of PFO closure, we report the changes of 5-HT in peripheral venous blood in 1-year follow-up. Method: 97 PFO-related stroke patients were recruited in accordance with IRB. Venous blood was collected at baseline (BL) and 1 year follow-up (FU) post treatment (PFO closure or medical therapy). Plasma 5-HT was quantified by mass spectrometry. Patients with serotonin modifying medications (e.g. SSRIs) or conditions (e.g. anxiety/depression) were excluded. Result: 5-HT concentration in peripheral venous blood was significantly reduced by 27.27% (BL: 7.57 ± 8.04 μmol/l; FU: 5.51 ± 5.72 μmol/l; p = 0.0034) in 61 patients receiving PFO closure (Fig 1A). In the 37 PFO patients treated with medical therapy alone, no changes were observed (5-HT: BL: 5.79 ± 7.15 μmol/l; FU: 6.25 ± 6.68 μmol/l; p = 0.4050) (Fig 1B). This decrease in serotonin was independently associated with PFO closure after adjusting for age, gender, medical history and medication status in a multivariate regression (Fig 1C). Conclusion: We found that PFO closure independently reduced 5-HT level in peripheral venous blood. These results support the hypothesis that PFO associated right-to-left interatrial shunting may foster higher levels of procoagulant and vasoactive substances in circulation. We have previously found PFO closure to decrease prothrombotic markers immediately post closure; this effect is now shown also to be sustained in long term follow-up up to 1 year. Further studies are ongoing on the clinical outcome of these PFO related stroke patients with respect to their prothrombotic circulatory profiles.
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